Bradykinin (BK) increases production of prostaglandin E-2 and prostacyclin and accumulation of cAMP in cultured human forskin fibroblasts. We have characterized the BK receptor and studied its autoregulation in intact fibroblasts. The number of binding sites was 230 (plus or minus) 18 (mean (plus or minus) SEM, n = 4) fmol/mg protein with a dissociation constant of 4.6 (plus or minus) 0.5 nM (mean (plus or minus) SEM, n = 4). The receptor is of the B2 type, based on relative potencies of BK analogs and peptides in competing for BK-binding sites. Potencies of peptides in displacing BK correlated with their ability to stimulate PGI-2 accumulation. Incubation of cells with 1 MuM BK for 5 min led to a marked reduction in the number of BK-binding sites as well as in the ability of BK to increase PGI production and cAMP content. The loss in BK receptor reflected an alteration in Bmax and not Kd. After brief incubation with BK, incubation without BK (30 min) almost completely restored Bk receptor number and BK-induced PGI-2 release. With longer exposure to BK, recovery was inversely related to the length of exposure and concentration of BK. Recovery was prevented by bacitracin which inhibited BK degradation. BK-degrading systems, in addition to other factors, play an important role in the autoregulation of the BK receptor and consequently cell responsiveness to BK.